Influence Of Resveratrol On The Expression Of β-amyloid Protein In Model Mice With Alzheimer's Disease

Objective:This study was designed to investigate the effect and the mechanism of resveratrol(Res) on the expression ofβ-amyloid protein(Aβ) in model Mice with Alzheimer's disease.Methods:According to the results of step-down test and body weight,120 Kunming female Mice were randomly divided into 4 groups:control group,AD model group,diethylstilbestrol(DES) group and resveratrol(Res) group.Res group was divided into three dose treatment groups. Every group had 20 Mice.Control group was given saline intraperitoneal injection and three distilled water intragastric administration.Other groups were established with D-galactose(120mg·kg^-1·d^-1) intraperitoneal injection and aluminum chloride (10mg·kg^-1·d^-1) intragastric administration.All these were made continuously for 90 days.Since the 31th day,control group and AD model group were treated with tri-distilled water intragastric administration.DES group was treated with diethylstilbestrol intragastdc administration.Res group was given Res intragastric administration 22 mg·kg^-1·d^-1,44 mg·kg^-1·d^-1,88 mg·kg^-1·d^-1 respectively.The treatment continued for 60 days.Subsequently,the learning and memory ability was tested by step-down test.The expression of Aβ₄₀,amyloid precursor protein(APP) and neuronal nitric oxide synthase(nNOS) in cerebral cortex were observed by immunohistochemistry staining method.The content of Malondialdehyde(MDA) and the activites of giutathione peroxidase(GSH-PX) and superoxide dismutase (SOD) in serum and brain tissue were measured.Nitric oxide synthase(NOS) activity and the level of nitric oxide(NO) in brain tissue were measured,while observing the changes of endometrium microscopically.Results:In AD model group,compared with control group,the learning and memory abilities lowered(P＜0.01),the expression of Aβ₄₀ and n.NOS in cerebral cortex increased,the activities of GSH-PX and SOD lowered,and the activities of NOS,constitutive nitric oxide synthase(cNOS) and the contents of MDA,NO increased obviously(P＜0.01).In the DES and Res groups,compared with AD model group,the learning and memory abilities increased(P＜0.05),the expression of Aβ₄₀ and nNOS in cerebral cortex were decreased,the activities of GSH-PX,SOD increased,cNOS activity and the contents of MDA and NO lowered(P＜0.05).Res groups showed a dose-dependent effect.The endometrium hyperplasia occurred in DES group,while the endometrial atrophy occurred in AD model group.There were some atypical changes in other groups.Conclusion:(1)Continuous oral administration of resveratrol could improve cognitive ability of AD model Mice.(2)Resveratrol can reduce the expression ofβ-amyloid protein in cerebral cortex of AD model Mice with dose-dependent,which may contribute to the resveratrol's inhibition of the production of oxygen radicals, the lipid peroxidation,the activity of neuronal nitric oxide synthase,reducing nitrogen monoxidum content.(3)Resveratrol showed the same effects on AD model Mice,campared with DES,and had no endometrial hyperplasia side-effect on AD model Mice.